574
J. Org. Chem., Vol. 40, No. 5, 1975
Middleton
2 N NaOH, brine), dried (MgSOd), and concentrated in uacuo. The residue, a red oil (7.4 g), was chromatographed on neutral I11 alumina made up in pentane. Elution by pentane gave 2.11 g which was discarded. Elution by ether gave 2-bis(tert- buty1thio)methylpyridine (3.05 g, 0.0113 mol, 11%)which was distilled in a short path apparatus: bp 80’ (0.1 mm); ir (film) 1588 (s), 1568 (m), 1470 (s), 1432 (s), 1364 (s), 1154 (s), 990 (m), 742 (m), 718 (m) cm-’; uv X max (MeOH) 271 mfi (6 4480); nmr (CDCl3) 6 8.42 (broad d, 1,J = 6 Hz), 7.64 (m, 2), 7.10 (q, l), 5.16 (8, l), 1.28 (s, 18). Anal. Calcd for C14H23NS2: C, 62.43; H, 8.61; N,5.20. Found C, 62.40; H, 8.95; N, 5.22. Pyridine (7.9 g, 0.1 M ) was treated with methyllithium (78 ml of a 1.60 M solution, 0.12 mol) and tert-butyl disulfide (17.8 g, 0.1 mol) in an analogous manner. The bulk of the products were water soluble, presumably 2-picoline. The material eluted from neutral I11 alumina by ether (0.91 g, 0.0034 M, 3%) was identical (ir, nmr, mass spectrum) with 2-bis(tert-buty1thio)methylpyridine prepared above. Comparison was also made by tlc (silica gel GF eluted by CHCla-ethyl acetate 4:l).
chloride, 931-59-9; phenyl disulfide, 882-33-7; dimethyl disulfide, 624-92-0; m-chloroperbenzoic acid, 937-14-4; trifluoroacetic anhydride, 407-25-0; ethyl 2-bromopropionate, 535-11-5; ethyl 4-bromobutyrate, 2969-81-5; butyl disulfide, 629-45-8; ethyl a-bromoisobutyrate, 600-00-0; ethyl bromoacetate, 105-36-2; Z-bis(tertbutylthio)methylpyridine, 53730-89-5;2-picoline, 109-06-8.
References and Notes
Acknowledgment. We wish to acknowledge the support and encouragement of Dr. Max Wilhelm and many helpful discussions with Mr. Louis Dorfman and Professor Peter Yates. We thank Mr. Dorfman’s staff for microanalyses
(1) H. L. Yale in “The Chemistry of Heterocyclic Compounds,” Vol. 14,A. Weissberger, Ed., “Pyridine and its Derivatives,” Part iV, E. Klingsberg, Ed., Wiley, New York, N.Y., Chapter XV. (2)H. M. Wuest and E. H. Sakel, J. Amer. Chem. SOC., 73, 1210 (1951). (3)L. L. Bambas, J. Amer. Chem. SOC., 67, 668 (1945). (4) H. Furst and H. J. Dietz, J. Prakt. Chem., 4, 147 (1956). (5) M. Heltzig, W. Gobel, and H. J. Konig, J. Prakt. Chem., 311, 174 (1969). (6) J. Delarge, Pharm. Acta Helv., 44, 637 (1969). (7) E. Plazek and E. Sucharda, Chem. Ber., 59, 2282 (1926). (8) R. D. Westland, R. A. Cooley, J. L. Holmes, J. S. Hong, M. H. Lin, M. L. Zwiesler, and M. M. Grenan, J. Med. Chem., 16, 319 (1973). (9)K. F. King and L. Bauer, J. Org. Chem., 36, 1641 (1971). (IO) C. S. Giam and J. L. Stout, Chem. Commun., 478 (1970). (11) R. Levineand W. M. Kadunce, Chem. Commun., 921 (1970). (12)C. S. Giam and J. L. Stout, Chem. Commun., 142 (1969). (13)G. Fraenkel and J. C. Cooper, TetrahedronLeft.. 1825 (1968). (14)C. S. Giam and E. E. Knaus, TetrahedronLett, 4961 (1971). (15)R. F. Francis, W. Davis, and J. T. Wisener, J. Org Chem., 39, 59
and spectra. R e g i s t r y No.-3a, 53730-69-1; 3b HC1, 53730-70-4; 3c, 5373071-5; 4a, 53730-72-6; 4b, 53730-73-7; 4c, 53730-74-8;5a, 53730-759; 5b, 53730-76-0; 5c, 53778-52-2; 6a, 53730-77-1; 6c, 53730-78-2; 7a, 53730-79-3; 7b, 53730-80-6; 712, 53730-81-7; 7d, 53730-82-8; 7e HCl, 53730-83-9; 7f, 53730-84-0;Sa, 53730-85-1;8b, 53730-86-2;9, 53730-87-3; 11, 53730-88-4; pyridine, 110-86-1; phenylsulfenyl
(16) N. Finch and H. W. Gschwend, J. Org. Chem., 36, 1463 (1971). (17)L. E. Tenenbaum, ref 1, Chapter V. (18)M. E. Kuehne, J. Org. Chem., 28, 2124 (1963). (19)Melting points were obtained in a Thomas-Hoover melting point apparatus and are uncorrected. Nmr spectra were obtained on a Varian A-60 instrument, infrared spectra on a Perkin-Elmer 21 or 521,mass spectra on an A MS902 at 70 eV, and ultraviolet spectra on a Carey 14 instrument.
(1974).
New Fluorinating Reagents. Dialkylaminosulfur Fluorides’ William J. Middleton Central Research Department, E. I. du Pont de Nemours and Company, Experimental Station, Wilmington, Delaware 19898 Received September 23,1974 Dialkylaminosulfur trifluorides (2) and bis(dialky1amino)sulfur difluorides (5) are easy to handle fluorinating reagents useful for replacing hydroxyl and carbonyl oxygen with fluorine under very mild conditions. The trifluorides (2) were prepared by the reaction of dialkylaminotrimethylsilanes (1) with SF4, and the difluorides (5) were prepared by the reaction of 2 with 1. These fluorides are particularly useful in fluorinating sensitive alcohols and aldehydes. For example, reaction of diethylaminosulfur trifluoride (DAST) with isobutyl alcohol gave isobutyl fluoride as the principal product, reaction of DAST with pivaldehyde at 25’ gave (CH3)zCCHFzin 78% yield, and reaction of Me2NSFzNEt2 with crotyl alcohol at 25’ gave crotyl fluoride in 78% yield. Sulfur tetrafluoride is a useful fluorinating agent for replacing oxygen with fluorine in organic compounds.2 T h e substitution of one or two of t h e fluorine atoms in sulfur tetrafluoride with dialkylamino groups would result in aminosulfur fluorides that also may be expected t o be fluorinating agents. We have examined t h e preparation and chemical properties of dialkylaminosulfur trifluorides and bis(dialky1amino)sulfur difluorides with t h e ,hope of developing new selective fluorinating reagents. Preparation. T h e dialkylaminosulfur trifluorides (2) were prepared by a n adaptation of a literature p r ~ c e d u r e , ~ which consists of treating sulfur tetrafluoride with a dialkylaminotrimethylsilane ( 1). Diethylaminosulfur trifluoride4 (DAST), dimethylaminosulfur trifluoride,3 and t h e new pyrrolidinosulfur trifluoride were prepared by this method. When this reaction is conducted in trichlorofluoromethane (bp 25’) at -70°, high yields of a product of very high purity are obtained, since the only appreciable by-product is fluorotrimethylsilane (3), an easily separated low-boiling (bp 17’) material. These three trifluorides are stable prod-
ucts that can be distilled and stored in plastic bottles at room temperature. &NSi(CH,), 1
+
SF,
-
bNSF,
+ FISi(CH,X
2
3
Diisopropylaminosulfur trifluoride (2, R2N = diisopropylamino) was also prepared, but i t was unstable to distillation and decomposed t o isopropyliminosulfur difluoride (4) when heated above 60’. (CHJ2CHN=SF, 4
RZN-SF2-NR’Z 5
Bis(dialky1amino)sulfur difluorides ( 5 ) have not been prepared previously. We prepared them by t h e reaction of a dialkylaminotrimethylsilane (1) with a dialkylaminosulfur trifluoride (2) at 25’. T h e sulfur difluorides were not stable to distillation, b u t they could be easily purified by removing t h e volatile solvent (CC13F) and by-product (3) by evaporation at reduced pressure. T h e I9F n m r spectra of
J. Org. Chem., Vol. 40, No. 5, 1975
Dialkylaminosulfur Fluorides
575
Table I Reaction@ of Alcohols with EtZNSF, Yield, Alcohol
Registry No.
Reaction solvent
Products
RegistryNo.
%b
Bp,
OC
(mm)
"F
nmr,
6 , ppm
1-Fluorooctanec 463-11-6 90 4 2 4 3 (20) -218.8 661 -53 -0 88 45-46 2 -Fluoro-2-methyl-139.2 butaned Isobutyl fluoridee 78-83-1 359-00-2 49 20-22 -221.4 353-61-7 21 10-12 tert-Butyl fluoridef -132.1 1-Fluoro-2 -isopropyl- 53731-15-0 50 40 (5) 1490-04-6 -175.9 Menthol B-methylcyclohexaneh Benzyl fluoride 462-06-6 100-51-6 CC13F 75 139 -207.5 Benzyl alcohol 1OF -207.5 Benzyl fluoride CH2C12 Benzyl alcohol* 53731 -16 -1 709 Cycloocty 1 fluoride -160.5 696-71 -9 CC13F Cyclooctanol 931 -88-4 3og C yclooctene 53731-17-2 75 43-44 115-19-5 2 -Fluoro-2 -methyl-129.3 2-Methyl-33 -butynej butyn-2 -01 624-72-6 70 25-27 107 -21 -1 CH30(CH2CH20),CH3 1 , 2 - D i f l u ~ r o t h a n e ~ -225.9 Ethylene glycol 3 -Fluoro-2,2 -dimethyl- 53731-18-3 74 Mp 93-94 -134.4 124-76-5 CC13F exo-Borneol bicycld2.2 .l]heptane' Camphene 18 3 -Fluoro-2,2-dimethyl507-70-0 CC1,F 72 Mp 93-94 -134.4 endo-Borneol bicyclo[2.2.l]heptane 17 Camphene 53731-19-4 78' 22-24 -171.6 598-32-3 CH30(CH2CH20)2CH33 -Fluoro-1 -butenem 3-Buten-2-01 53731-20-7 2 2g -210.0 1-Fluoro-2-butene" Isooctane 9 18 3-Fluoro-1 -butene 3-Buten-2-01 9g 1-Fluoro-2 -butene 6117-91-5 CH30(CH2CH2O),CH33 -Fluoro-1 -butene 72g 2-Buten-1-01 2 8' 1-Fluoro-2-butene Isooctane 64g 3 -Fluoro-1 -butene 2-Buten-1 -01 1-Fluoro-2-butene 3 6g 762-49-2 70 72 -213.4 2 -Bromoethanol' 540-51 -2 CH30(CH2CH20)2CH31-Bromo-2-fluoroethane 762-50-5 69 50-53 -219.8 2 -C hloroethanol 107-07 -3 CH30(CH2CH20)2CH31-Chloro-2-fluoroethane' 349-43-9 78 50-51 (50) -184.6 Ethyl 2-fluoroproEthyl lactate 97 -64 -3 CHZC12 pionate 53731 -14 -9 CC1,F 24021 -14-5 60 4 Ethyl CY -f luoronaph-178.4 Ethyl 1-naphthaleneacetateP thy leneglycolate 60-12-8 CH2ClZr 2 -Fluoroethyl458-87-7 60 68-69 (25) -215.2 2 -P heny 1benzeneS ethanol a All reactions were carried out between -50 and -78" unless otherwise noted. * Yield of isolated products unless otherwise noted. CY. Kobayashi, C. Akashi, and K. Morinaga, Chem. Pharm. Bull., 1784 (1968). K. Wiechart, C. Gruenert, and H. J. Preibisch, 2. Chen., 8, 64 (1968). e M. Moissan, J . Chem. SOC.,931 (1888).f K. A. Cooper and E. D. Hughes, J . Chem. Sac., 1183 (1937).g Product was not isolated in pure state. Yield is based on glc analysis. h Anal. Calcd for CloHlsF: F, 12.01. Found: F, 12.12. MezNSF3 used in place of EtZNSF3. 'Anal. Calcd for CBH~F: C, 73.4; H, 7.2; F, 19.4. Found: C, 73.7; H, 7.3; F, 19.2 A. L. Henne and M. W. Renoll, J. Amer. Chem. SOC., 58, 887 (1936).1 M. Hanack, Chem. Ber., 94, 1082 (1961). Anal. of sample separated by glc. Calcd for C4H7F: C, 64.8; H, 9.5; F, 25.6. Found: C, 65.0; H, 9.5; F, 25.5. nAnal. of sample separated by glc. Calcd for C4H7F: C, 64.8; H, 9.5; F, 25.6. Found: C, 65.0; H, 9.5; F, 25.5.0 W. F. O ~72.4; : H, 5.6; F, 8.2. Found: C, 72.5; H, 5.7; F, Edge11 and L. Parts, J . Amer. Chem. Soc., 77, 4899 (1955). PAnal. Calcd for C I ~ H I ~ F C, 7.9. qlviscous oil, nZ5D 1.5788, purified by chromatography over silica (CHC13). Reaction temp was 40". C. H. DePuy and C. A. Bishop, J. Amer. Chem. SOC.,82,2535 (1960). 1-0ctanol 2 -Methyl-2but ano 1 Isobutyl alcohol
111-87-5 75 -85 -4
the difluorides at -80' and at 30" show a single sharp resonance at 5 t o 10 p p m downfield from CC13F. This relatively high field absorption and lack of spin-spin coupling indicate that both fluorine atoms are equivalent a n d are probably in t h e axial position. These spectra are in contrast t o the spectra of the trifluorides (2), which show both equatorial and axial fluorines coupled to each other.5 Fluorinations with A m i n o s u l f u r Fluorides Markovskij, Pashinnik, and Kirsanovc recently reported that the dialkylaminosulfur trifluorides are useful-in replacing carbonyl oxygen of aldehydes and ketones with fluorine. T h e work that we have done independently fully supports these observations. In addition, we have found that t h e dialkylaminosulfur trifluorides are perhaps even
more useful in replacing the hydroxyl groups of sensitive alcohols with fluorine, and t h e bis(dialky1amino)sulfur difluorides are also useful reagents for preparing organofluorine compounds. F l u o r i n a t i o n of Alcohols The reaction of DAST and the other dialkvlaminosulfur trifluorides with alcohols to replace t h e hydroxyl group with fluorine appears t o be a broadly general reaction with distinct advantages over other reagents used for this purpose, including SF4,7 SeF4 pyridine,8 a-fluorinated a r n i n e ~ a, n~ d HF and HF-amine reagent^.^ Primary, secondary, and tertiary alcohols all react, with high yields of the unrearranged fluoride usually resulting. These reactions can be conducted under very mild condi-
-
576 J. Org. Chern., Vol. 40, No. 5, 1975
Middleton
tions so t h a t other groups, including ester groups and other halogens, can also be present. Typically, the alcohol can be added slowly t o a solution of DAST in an inert solvent cooled t o -50 t o -78'. For many alcohols, the reaction occurs rapidly even at this low temperature. Diglyme is a convenient solvent for the preparation of low-boiling fluorides because the product can be distilled out of the reaction mixture and t h e H F t h a t is formed in the reaction remains behind complexed with the diglyme. For the preparation of higher boiling fluorides, lower boiling solvents such as pentane, methylene chloride, or trichlorofluoromethane are useful. Table I contains a list of the alcohols t h a t have been converted t o fluorides. Two problems can occur when replacing the OH groups of an alcohol with fluorine: carbonium ion type rearrangements and dehydration. T h e carbonium ion type rearrangements are less likely t o occur when DAST is used than when other known fluorinating agents are used. For example, fluorination of isobutyl alcohol with DAST gave more than a 2:1 ratio of isobutyl fluoride (6) t o tert-butyl fluoride, whereas fluorination with SeF4 pyridine is reported8 t o give only t h e rearranged tert- butyl fluoride. However, t h e more easily rearranged ero- and endo-borneo1 gave the rearranged fluoride 7.
-
DAST
DAST
+
-
(CH3)2CHCH20H (CH,),CHCH2F 4Wo
+
+
(CH3),CF
EtzNSOF
+ HF
21%
+ OH
F 7
Dehydration (elimination) also appears t o be less of a problem with DAST than with other fluorinating reagents. For exampIe, cyclooctanol reacts with DAST t o give a 70:30 ratio of cyclooctyl fluoride (8) t o cyclooctene, whereas EtzNCFzCHClF reacts t o give only cyclooctene.
+
DAST
()-OH
--t
OF0 +
70%
30%
8
CH,CH= CHCH,OH 9
or CH3CHOHCH=CH2
+ DAST
CHBCH-CHCHZF 10
11-10. Reaction of DAST with crotyl alcohol in a less polar solvent (isooctane) gave larger amounts of 10 (36%), but still gave the rearranged 11 as the major product (64%). Fluogave the rination of the isomeric alcohol, 3-buten-2-01 (E), same two products, but in different ratios (see, Table I). Since both 9 and 12 should form the same carbonium ion, it appears t h a t a free carbonium ion is not involved in the reaction, but from the rearranged products observed in these reactions and in the reactions with borneol, it is clear t h a t these fluorination reactions do have considerable carbonium ion character. The bis(dialky1amino)sulfur difluorides (5) are also useful reagents for replacing hydroxyl groups with fluorine in sensitive alcohols. Although they are less reactive, the difluorides have certain advantages over the trifluorides in t h a t they cause less rearrangement and elimination. For example, diethylaminodimethylaminosulfur difluoride (5, R = CH3; R' = C2H5) reacts with crotyl alcohol (9) t o give t h e unrearranged 10 as the principal product, with only smaller amounts of the rearranged 11 formed (ratio 72:21). The difluorides 5 also cause less dehydrations of easily dehydrated alcohols, such as cyclohexanol, as compared t o the reaction of the same alcohols with the trifluorides (2). The smaller amounts of rearrangement and dehydration products t h a t are formed in the fluorination of alcohols with the difluorides 5, as opposed t o the trifluorides 2, can be rationalized by assuming t h a t both reactions go through a n unisolated intermediate in which one of the fluorines on sulfur has been replaced by a n alkoxide group (13).This intermediate could then dissociate t o give an ion pair consisting of a carbonium ion and a sulfur oxide anion (14). T h e sulfur oxide ion containing two amino groups (14, X = NR2) would be expected t o lose fluoride more readily than the anion containing only one amino group (14,X = F), and therefore have a shorter lifetime. Since the ion pair formed in the reaction of the difluoride 5 with an alcohol would have a shorter lifetime than the ion pair formed from 2 and an alcohol, less carbonium ion type reactions would occur. An alternate explanation would be based on leaving group ability instead of fluoride ion transfer. Since the leaving ability of R2NSF20- should be greater than (RzN)zSFO-, the decomposition of intermediate 13 (X = F) t o give products should involve more carbonium ion character than decomposition of 13 (X = NRz), and therefore would be subject t o more extensive rearrangement and elimination.
F
I
RO-S--NR,
-+
I
-
12
high yield of monofluorides consisting of a 7228 ratio of
X 13, X = F, NR,
+ CHACHCHcCH2 I
F 11
Crotyl alcohol (9) is sensitive t o both double-bond rearrangement and dehydration. For example, it reacts with SF4 t o give a 90% yield of butadiene, a 9% yield of 3-flUOrO1-butene (ll),and only a trace of crotyl fluoride (10).Reactions of DAST with crotyl alcohol under t h e same conditions (diglyme solvent) gave virtually no butadiene and a
14, X = F, NR?
Fluorination of Aldehydes and Ketones. DAST is a convenient reagent for replacing the carbonyl oxygen of aldehydes and ketones with two fluorine atoms (See Table 11). This reagent is particularly useful for fluorinating aldehydes and ketones t h a t are sensitive t o acidic conditions or contain other functional groups t h a t are unstable in the presence of acid, since no acid other than adventitious H F is formed in the reactions and no additional acidic catalyst is needed. Even aqueous work-ups do not result in the formation of acidic solutions, since t h e only by-product, diethylaminosulfinyl fluoride (15), is hydrolyzed t o give sulfur dioxide and diethylamine hydrofluoride.
J.Org. Chem., Vol. 40, No. 5, 1975 577
Dialkylaminosulfur Fluorides
Table I1 Reactions of Carbonyl Compounds with D A S T Carbonyl compd
Isovaler a!de hyde P r opionaldehyde Pivaldehyde Pivaldehyde Benzaldehyde 1-Naphthaldehyde 4-Heptanone Acetophenone
Registry No.
Reactim solveiat
T:?p,
Time
Product
%
590-86-3 CC1,F
25 30 min 1,l-Difluoro-353731-22-9 methylbutane 123-38-6 CC1,F 25 30 min 1,l-Difluoro430-61-5 propane 630-19-3 CC1,F 25 1 h r (CH3),CCHFZb 53731-23-0 Diglyme 25 1 h r (CH,),CCHFz CH~=IC(CH,)CHFCH~~ 53731-24-1 FC(CH,)ZCHFCH,' 53731-25-2 100-52-7 CHZCIz 25 2 h r Benzal fluoride0 455-31-2 66-77-3 CHZC1,
25 18 h r 25 7 day 85 20 h r
123-19-3 CC1,F 98-86-2 Elyme
53731-21-8 Benzene 78 24 h r
O+O
Isolated yield,
Registry No.
80
Bp (mp), 'C
59-60
19F nmr, 6 , ppm
-115.5
95"
-118.2
78 47-48 24 47-48 26 51-52 31 65-66 75 57 (35 m m ) 1-(Difluoromethy1)53731-26-3 72 78-79 naphthy lenef (0.4 m m ) 4 , 4 - D i f l ~ o r o h e p t a n e ~ 5373 1-27 -4 68 110-111 1,l-Difluoroethyl10541-59-0 66 64-65 benzeneh (40 mm)
-128.6 -128.6 -174.4 -152.0, -185.5 -110.9
&&.;
53731-28-5 60' (106-109)
-86.2, -86.6
53731-29-6 15'
-80.9, -81.0
Me
-111.1 -98.6 -87.7
Me
(145-150)
Me
Glc yield. *Anal. Calcd for C8HloF2: C, 55.5; H, 9.3; F, 36.1. Found: C,"55.7;H, 9.4; F, 35.0. C A n d Calcd for CsHeF: C, 68.2; H, 10.3; F, 21.6. Found: C, 68.3; H, 10.5; F, 21.8. d A n ~ lFound: . C, 65.3; H, 9.5; F, 35.4. e W. R.Hasek, W. C. Smitjl, and V. A. Engelhardt, J.Amer. Chem. Soc., 82, 643 (1960). f Anal. Calcd for C11HaF: C, 74.1; H, 4.5; F, 21.3. Found: C, 74.2; H, 4.2; F, 21.2. #Anal. Calcd for C,H14F2: C, 61.7; H, 10.4; F, 27.9. Found: C, 62.1; H, 10.2; F, 28.1. h K.Matsuda, J. A. Sedlak, J. S. Noland, and G. C. Cleckler, J Org. Chem., 27, 4015 (1962). "nul. Calcd for CloH14F.1: C, 57.1; H, 6.7; F, 36.1. Found: C, 57.1; H, 6.8; F, 36.1. j Purified by chromatography on A1203 (pentane-ether). Anal. Calcdfor C10H14F20:C, 63.8; H, 7.5; F, 20.2. Found: C, 63.1; Ih 7.3; F, 20.9. a
Scheme I
Table I11 Effect of Solvent on P r o d u c t Distribution in the Fluorination of Pivaldehyde with D A S T CHpC(CH3)
-
FC(CH3)z.
( C H ~ ) ~ C C H F ZCHFCH3
CC13F
Pentane CC13H CHZC1, Xylene Tetrahydrofuran Pivaldehyde Diglyme
88 87 72 72 64 65 60 30
II
(CH3)&XH
% of produc$ (glc yields)
Solvent
0 16
H
I 5 (CH,)&C--OH I F
H
I
DAST __*
(CH&CF-OSF2NEt,
CHFCH3
2 3 3 2 8 20 10 32
10 10 25 26 28 15 30 38
H [CH3---i-i-CH.+
I
%FzNEtz + -
[ 1I -
nonpolar Solvent
solvent
1
(CH,),CC+ OSFzNEtz
0 RZC-0
+ DAST
RzCFz
+
EtZN-SF 15
II
Pivaldehyde (16) is an example of an acid-sensitive aldehyde. Previous attempts to prepare the corresponding gemdifluoride have resulted in rearrangements or trimerization. However, pivaldehyde can be successfully fluorinated to 17 by t h e use of DAST in a nonpolar solvent such as pentane or CC13F. Carbonium ion type rearrangements will occur, however, if more polar solvents are used (See Table 111). Thus, if diglyme (a basic, polar solvent) is used, the rearranged products 18 and 19 are formed, a n d if chloroform is used (a nonbasic, polar solvent), considerable rearrangement product 19 is formed, but only a small amount of t h e elimination product 18 is formed. T h e solvent dependancy of this reaction is consistent with t h e reaction shown in Scheme I.
18
19
Experimental Sectionlo Dialkylaminosulfur Trifluorides (Table IV). The four trifluorides listed in Table IV were prepared by the reaction of an aminotrimethylsilane with sulfur tetrafluoride in CClsF, as illustrated by the preparation of diethylaminosulfur trifluoride (DAST). A solution of 96 g (0.66 mol) of diethylaminotrimethylsilanein 100 ml of CC13F was added dropwise to a solution of 40 mi (measured at -78O, 0.72 mol) of sulfur tetrafluoride in 200 ml of CC13F at -65 to -6OO. The reaction mixture was warmed to room temperature and then distilled to give 88.9 g (84%) of DAST as a pale yellow liquid. Bis(dialky1amino)sulfur Difluorides (Table IV). The four
578
J.Org. Chem., Vol. 40, No. 5, 1975
Middleton
Table IV Aminosulfur Fluorides Carbon,%
%
Compd
(CH,),NSF, (c~H,),NsF,
Registry No.
Bp, 'C ( m m )
'?F nmr, 6
, ppm yield
Calcd Found
Hydrogen,%
Fluorine, %
Calcd Found Calcd
Found
Nitrogen, % Calcd
Found
Sulfur, % Calcd Found
3880-03-3 49-49.5 (33) 19.7, 59.2 18.0 18.3 4.6 4.7 42.8 42.6 10.5 10.7 24.1 23.8 38078-09-0 46-47 (10) 31.2, 55.5 84 29.8 30.0 6.3 6.4 35.4 35.1 8.7 8.5 19.9 19.7 53731-09-2
54-55 (15)
[(GH3),CB1,NSF3 (CH31zNSF2N(CH3), (CH3)zNSF,N(C,H,), (CzH5)zNSFzN(C2H5)2
50713-80-9 53731-10-5 53731-11-6 53731-12-7
a
GH.UJSF~N(-J
53731-13-8 Mp25-26
Mp 64-65.5 a a
83 30.2 29.9 5.1 5.3 35.8 35.5 6.9 10.9 9.7 5.9
8.8
8.8 20.1 20.0
99a 30.1 29.9 60 30.4 30.5 7.7 7.9 24.0 24.1 17.7 17.6 20.3 19.7 92b 20.4 20.4 92b 17.7 17.9 99
44.7 44.5 3.2 3.1 20.2 20.0
aNot distilled. *Crude yield.
difluorides listed in Table IV were prepared by the reaction of dimethylaminosulfur trifluoride or DAST with an aminotrimethylsilane, as illustrated by the preparation of bis(dimethy1amino)sulfur difluoride. A 29.25-g (0.25 mol) sample of dimethylaminotrimethylsilane was added dropwise to a solution of 33.2 g (0.25 mol) of dimethylaminosulfur trifluoride in 100 ml of CC13F cooled to -78'. The reaction mixture was warmed to 25O and then filtered under nitrogen to remove a small amount of suspended solid. The filtrate was evaporated to dryness under reduced pressure to give 23.5 g (60%) of bis(dimethy1amino)sulfur difluoride as a white crystalline solid. N-Isopropyliminosulfur Difluoride (4). Attempted distillation of crude diisopropylaminosulfur trifluoride caused this product to decompose a t about 60' (2 mm). The volatile decomposition products were collected in a cooled trap and redistilled to give an 80% yield of 4 as a light yellow liquid: bp 63O; l9F nmr (CCl3F) 6 72.9 ppm; lH nmr (CC13F) 6 1.28 ppm (d, J = 6.5 Hz, 6 H) and 4.17 ppm (septet,J = 6.5 Hz, 1H). Anal. Calcd for C ~ H ~ F Z NC, S :28.3; H, 5.6; F, 29.9; N, 14.0; S, 25.2. Found: C, 28.4; H. 5.6; F, 29.5; N, 14.0; S, 25.4. Fluorination of Alcohols (Table I). The alcohols listed in Table I were added to a solution of DAST or dimethylaminosulfur trifluoride in an inert solvent cooled to -50 to -78'. The reaction mixture was then warmed to room temperature or higher. An initial exothermic reaction usually occurred a t low temperature. In some cases, a second exothermic reaction was evident during the warm-up period. The lower-boiling product fluorides were distilled out of the reaction mixture at reduced pressure. Reaction mixtures containing higher-boiling fluorides were mixed with water, and the organic layer was separated and dried, and the solvent was distilled off. The product fluorides were purified by distillation, recrystallization, or column chromatography. The following are representative examples. Ethyl 2-Fluoropropionate. A solution of 1.18 g (0.01 mol) of ethyl lactate in 2 ml of methylene chloride was slowly added to a solution of 1.25 g (0.01 mol) of DAST in 5 ml of methylene chloride cooled to -78'. The reaction mixture was warmed to room temperature and mixed with cold water. The lower layer was separated, washed with water, dried (MgS04), and distilled to give 0.93 g of ethyl 2-fluoropropionate1°as a colorless liquid. 1-Bromo-2-fluoroethane. Ethylene bromohydrin, 31.25 g (0.25 mol), was added dropwise to a solution of 33 g (0.25 mol) of dimethylaminosulfur trifluoride in 150 ml of diglyme cooled to -50'. The reaction mixture was warmed to room temperature, and 50 ml of the most volatile portion was distilled out at reduced pressure. The distillate was mixed with water, washed with 5% sodium bicarbonate solution, dried (MgSOJ, and redistilled to give 22.2 g of 1bromo-2-fl~oroethane~~ as a colorless liquid. Fluorination of Crotyl Alcohol with (Diethylamino)(dimethylamino)sulfur Difluoride. A solution of 1.44 g (0.02 mol) of crotyl alcohol (2-buten-1-01) in 2 ml of diethylene glycol dimethyl ether was slowly added to a stirred solution of 3.7 g (0.02 mol) of (diethylamino)(dimethylamino)sulfur difluoride in 10 ml diethylene glycol dimethyl ether cooled to -78'. The reaction mixture was warmed to 25O and the volatile products were distilled out under reduced pressure to give 1.3 ml of colorless liquid. Redistillation gave 1.06 g (72%) of a mixture containing 79% l-fluoro-2-
butene (crotyl fluoride) and 21% 2-fluoro-3-butene, bp 24-27O. When the reaction was repeated, using isooctane in the place of diethylene glycol dimethyl ether as the reaction solvent, a 65% yield of fluorobutene was obtained consisting of 87% l-fluoro-2butene and 13902-fluoro-3-butene. Fluorination of Alcohols with (Me2N)ZSFz. A solution of 1.08 g (0.01 mol) of benzyl alcohol in 2 ml of methylene chloride was added slowly to a solution of 0.0066 mol of bis(dimethy1amino)sulfur difluoride in 6 ml of methylene chloride cooled to -78'. The reaction mixture was warmed to room temperature and mixed with water. The organic layer was separated, washed with water, and then 5% sodium bicarbonate, and dried (MgS04). Analysis by glc and 19Fnmr showed that benzyl fluoride had been formed in 91% yield. Cyclohexanol was fluorinated in a similar manner to give fluorocyclohexane, 19Fnmr (CC13F) 6 -161.2 ppm (m). Fluorination of Aldehydes and Ketones with DAST (Table 11). The ketones and aldehydes in Table I1 were fluorinated by stirring them in an inert solvent with DAST at temperatures and for times indicated. The fluorinated products were isolated by pouring the reaction mixture into water, and then separating, drying, and distilling the organic layer. The following example illustrates this procedure. Fluorination of Isovaleraldehyde. A 1.72-g (0.02 mol) sample of isovaleraldehyde was slowly added to a solution of 2.5 ml (0.02 mol) of DAST in 10 ml of CClaF at 25'. The reaction mixture was stirred for 30 min, and then mixed with 25 ml of water. The lower organic layer was separated, washed with water, dried (MgSOd), as and distilled to give 1.73 g (80%)of l,l-difluoro-3-methylbutane a colorless liquid. Anal. Calcd for C ~ H I ~C, F 55.5; ~ : H, 9.3; F, 35.1. Found: C, 55.8; H, 9.6; F, 35.1. Registry No.-1 (R = Me), 2083-91-2; 1 (R = Et), 996-50-9; 1 [Rz = -(CH2)4-], 15097-49-1; 1 (R = Pri), 17425-88-6; 4,53731-081; sulfur tetrafluoride, 7783-60-0.
References and Notes (1) (a) Portions of this paper were presented at the Second Winter Fluorine Conference. St. Petersburg, Fla., Feb 1974: (b) Contribution No. 2193. (2) W. C. Smith, Angew. Chem., Int. Ed. Engl., 1, 467 (1962). (3) G. C. Demitras, R. A. Kent, and A. G. MacDiarmld, Chem. I d . (London), 41, 1712 (1964). (4) S. P. von Halasz and 0.Glemser, Chern. Ber., 104, 1247 (1971). (5) D. G. lbbott and A. F. Janzen, Can. J. Chem., 50,2428 (1972). (6) L. N. Markovskij. V. E. Pashinnik, and A. V. Kirsanov, Synthesis, 787 (1973). (7) W. A. Sheppard and C. M. Sharts, "Organic Fluorine Chemistry," W. A Benjamin, New York, N.Y., 1969. (8) G. A. Oiah, M. Nojlma, and I. Kerekes, J. Amer. Chern. SOC., 06, 925 (1974). (9) G. A. Olah, M. Nojima, and I. Kerekes, Synthesis, 786 (1973). IO) Melting points and boiling points are uncorrected. I9F nmr spectra were obtained with a Varian A56-60 spectrometer. Peak center positions are reported in parts per milllon downfield from CChF used as an internal reference. The dialkylaminosilanes used were prepared by the reactlon of secondary amines with trimethylchlorosilane. 11) J. A. Brocks, R. Kosfeld, P. Sartori, and M. Schmeisser, Chem. Ber., 1962 (1970). 12) F. L. M. Pattison, D. A. V. Peters, and F. H. Dean, Can. J. Chsm., 43, 1689 (1965).
